Design and Development of Graphene Oxide Nanoparticle/Chitosan Hybrids Showing pH-Sensitive Surface Charge-Reversible Ability for Efficient Intracellular Doxorubicin Delivery

Abstract

A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π-π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug delivery system with positive surface charge by taking advantage of the pH difference between physiological conditions and the tumor microenvironment to enhance the cellular uptake. Then, the pH-dependent site-specific drug release was realized. The in vitro investigations confirmed that these promising GON/CS/CS-DMMA hybrids with the charge-reversible character possessed various merits including excellent encapsulation efficiency, high stability under physiological conditions, enhanced cellular uptake by HepG2 cells, and tunable intracellular chemotherapeutic agent release profiles, proving its capability as an intelligent anticancer agent nanocarrier with enhanced therapeutic effects. This smart GON/CS/CS-DMMA vehicle with the surface charge-reversible character may be used as a significant drug delivery system for cancer treatment.

Functionalized Graphene Derivatives: Antibacterial Properties and Cytotoxicity

“…With particular regard to the fields of application that include food quality control and medicine field applications, the antibacterial features [8] and the biocompatibility properties toward the real matrixes (as food or normal human cell lines, organic tissue, and blood) represent a key point that nanomaterials must possess. There are several cases of study, described in literature by interesting review articles concerning the improved antibacterial activity [9] and the increased biocompatibility [10] properties, exhibited by the graphene derivatives. These last properties mainly depend on the synthesis routes applied for graphene production [11].…”

PEGylated hollow pH‐responsive polymeric nanocapsules for controlled drug delivery

“…In DDSs based on smart HNCaps, an encapsulated drug can be released owing to response to external triggers such as pH, temperature, electric field and ionic strength . Among these stimuli, the design and development of pH‐responsive DDSs are of particular of interest due to the simplicity and efficiency of this stimuli in comparison with others . In addition, it is worth noting that cancerous tissues have lower pH values than those of the surrounding normal tissues, which originate from abnormal metabolism of these tissues .…”

“…ammonium salt) or acidic (e.g. carboxyl) functionalities, which can either accept or release protons in response to pH changes, accompanying reversible variation in volume, solubility and equipoise between the extended and collapsed states . In this context, poly(acrylic acid) (PAA) is a well‐known pH‐responsive polymer with a pendent carboxyl group in each repeat unit and has received a great deal of interest due to its superior physicochemical as well as biological features …”

<p>Design and Characterization of Chitosan-Graphene Oxide Nanocomposites for the Delivery of Proanthocyanidins</p>

“…6 Nanoparticles have mainly been used for the simultaneous release of genes and chemotherapy drugs. [12][13][14] Although such carriers are useful for the transport of chemical compounds, no studies have immobilized phytodrugs on GO-CS nanoparticles.…”